Epinecidin-1 protects mice from LPS-induced endotoxemia and cecal ligation and puncture-induced polymicrobial sepsis
| Autor: | Chwan-Deng Hsiao, Bor Chyuan Su, Tai Wen Lin, Han Ning Huang, Jyh-Yih Chen |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Fish Proteins
Lipopolysaccharides 0301 basic medicine Lipopolysaccharide MAP Kinase Signaling System medicine.medical_treatment 030106 microbiology Lipopolysaccharide Receptors Inflammation Pharmacology Lung injury Biology Protective Agents Cell Line Sepsis Mice 03 medical and health sciences chemistry.chemical_compound Anti-Infective Agents medicine Animals Macrophage Receptor Cecum Ligation Molecular Biology Protein kinase B NF-kappa B medicine.disease Bacterial Load Endotoxemia Mice Inbred C57BL Toll-Like Receptor 4 Disease Models Animal RAW 264.7 Cells 030104 developmental biology Cytokine chemistry Immunology Cytokines Molecular Medicine Female lipids (amino acids peptides and proteins) medicine.symptom Reactive Oxygen Species Antimicrobial Cationic Peptides |
| Zdroj: | Publons |
| ISSN: | 0925-4439 |
| Popis: | The antimicrobial peptide, epinecidin-1 (Epi), was identified from Epinephelus coioides and may have clinical application for treating sepsis. Epi has been shown to ameliorate antibiotic-resistant bacteria-induced sepsis in mice, but further evaluation in mixed-flora models and a description of the protective mechanisms are essential to establish this peptide as a potential therapeutic. Therefore, we first tested the protective effects of Epi against polymicrobial sepsis-induced bactericidal infection, inflammation and lung injury that result from cecal ligation and puncture in mice. Furthermore, since lipopolysaccharide (LPS) is a key inducer of inflammation during bacterial infection and sepsis, we also tested the LPS-antagonizing activity and related mechanisms of Epi-mediated protection in mice with LPS-induced endotoxemia and LPS-treated Raw264.7 mouse macrophage cells. Epi rescued mice from both polymicrobial sepsis and endotoxemia after delayed administration and suppressed both lung and systemic inflammatory responses, while attenuating lung injury and diminishing bacterial load. In vitro studies revealed that Epi suppressed LPS-induced inflammatory cytokine production. Mechanistically, Epi disrupted the interaction between LPS and LPS binding protein, competed with LPS for binding on the cell surface, and inhibited Toll-like receptor 4 endocytosis, resulting in inhibition of LPS-induced reactive oxygen species/p38/Akt/NF-κB signaling and subsequent cytokine production. Overall, our results demonstrate that Epi is a promising therapeutic agent for endotoxemia and polymicrobial sepsis. |
| Databáze: | OpenAIRE |
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